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Alzheimer's Imaging Consortium.

Alfie Wearn1, Christine L Tardif2,3, Ilana R Leppert3,4

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|December 23, 2025
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Summary
This summary is machine-generated.

Locus coeruleus (LC) integrity is linked to amyloid and tau pathology in asymptomatic Alzheimer's disease (AD) individuals. This suggests the LC plays a key role in early AD pathogenesis.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Radiology

Background:

  • The locus coeruleus (LC) is an early site of tau pathology in Alzheimer's disease (AD), preceding clinical symptoms.
  • Investigating LC integrity in relation to amyloid and tau deposition is crucial for understanding early AD.
  • Asymptomatic, at-risk older adults provide a unique window into preclinical AD changes.

Purpose of the Study:

  • To determine the association between locus coeruleus (LC) integrity and in vivo cortical amyloid and tau deposition.
  • To explore these relationships in asymptomatic individuals with a familial risk for AD.
  • To assess potential longitudinal changes and modulatory effects of amyloid on tau-LC associations.

Main Methods:

  • Utilized MRI (T1w, neuromelanin-sensitive) and PET imaging (18F-NAV4694, 18F-flortaucipir) in 208 healthy older adults (PREVENT-AD cohort).
  • Quantified cortical amyloid and tau using SUVR and LC integrity via LCCNR.
  • Employed robust linear mixed-effects models and linear regression, with FDR correction for multiple comparisons.

Main Results:

  • Negative associations were found between LC integrity and cortical amyloid across most regions.
  • Cortical tau associations with LC integrity were localized to temporal and inferior parietal regions.
  • These associations were primarily observed at baseline, with no significant longitudinal effects. Global amyloid modulated the tau-LC relationship.

Conclusions:

  • Locus coeruleus degeneration correlates with increased amyloid and tau pathology in asymptomatic individuals at risk for AD.
  • These findings support the model of the LC as a central component in the earliest pathophysiological stages of AD.
  • The LC's integrity is a potential biomarker for early AD-related changes.